Autoimmune mechanisms have been described for a number of central nervous system diseases, and it has been suggested that schizophrenia shares several clinical, epidemiological, and genetic characteristics with them. Abnormal immunologic measures typical of diseases such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis have also been demonstrated in schizophrenia and provide another indirect link between schizophrenia and an autoimmune pathogenesis. The history of the search for immunological stigmata in schizophrenia, however, has been a controversial one, with a number of intriguing findings which have failed to find replication. The present Revised Application in the SMALL GRANT category is an attempt to demonstrate and correlate aberrant serum and CSF interleukin levels, increased CD5+ B Cells, and anti-brain antibodies in the same group of seventy-two hospitalized schizophrenic patients. Patients with bipolar disorder and healthy individuals will be studied as controls. The effects of serum prolactin and neuroleptic medication on the immunologic measures will be examined. In the revised submission, focus is placed on the efforts to examine a larger sample of patients and psychiatric controls to extend our previous finding that 40% of schizophrenic patients studied had serum IgG antibodies to the 60- kilodalton PI mitochondrial heat shock protein. Studies to correlate this specific finding with other putative autoimmune parameters will be undertaken. It is hypothesized that the co-occurrence of a number of such autoimmune-associated findings in the same subgroup of schizophrenic patients in this pilot project would support a theory of autoimmune pathogenesis and would suggest directions for future research.